Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and <i>KMT2A</i>-rearranged AML

Menghrajani, Kamal; Gomez-Arteaga, Alexandra; Madero-Marroquin, Rafael; Zhang, Mei‐Jie; Bo-Subait, Khalid; Sánchez, J. Ortiz; Wang, Hailin; Aljurf, Mahmoud; Assal, Amer; Bacher, Ulrike; Badawy, Sherif M.; Bejanyan, Nelli; Bhatt, Vijaya Raj; Bredeson, Christopher; Byrne, Michael; Castillo, Paul; Černý, Jan; Chhabra, Saurabh; Ciurea, Stefan O.; DeFilipp, Zachariah; Farhadfar, Nosha; Gadalla, Shahinaz M.; Gale, Robert Peter; Ganguly, Siddhartha; Gowda, Lohith; Grunwald, Michael R.; Hashmi, Shahrukh K.; Kanakry, Christopher G.; Kansagra, Ankit; Khimani, Farhad; Krem, Maxwell M.; Lazarus, Hillard M.; Liu, Hongtao; Martino, Rodrigo; Michelis, Fotios V.; Nathan, Sunita; Nishihori, Taiga; Olsson, Richard F.; Reshef, Ran; Rizzieri, David A.; Rowe, Jacob M.; Savani, Bipin N.; Seo, Sachiko; Sharma, Akshay; Solh, Melhem; Üstün, Celalettin; Verdonck, Leo F.; Hourigan, Christopher S.; Sandmaier, Brenda M.; Litzow, Mark R.; Kebriaei, Partow; Weisdorf, Daniel J.; Zhang, Yanming; Tallman, Martin S.; Saber, Wael

doi:10.1182/bloodadvances.2021004881

Cited by 7 publications

(2 citation statements)

References 35 publications

(42 reference statements)

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“…Allo-HSCT in CR1 was associated with improved OS (52% at 5 years vs 14% for those without allo-HSCT, p < 0.0001) [ 40 ]. The 5-year OS was 42% and the 5-year RI was 37% ( n = 426) for patients with the MLL rearrangement post-HSCT in the CIBMTR database [ 41 ]. The 1-year OS for the 7 patients (2 patients in NR before transplantation) with the MLL rearrangement or MLL-PTD was 83.3% (95% CI, 46.5–100%).…”

Section: Discussionmentioning

confidence: 99%

Addition of venetoclax to myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in high-risk AML

et al. 2023

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Background Venetoclax monotherapy is an effective option for patients with acute myeloid leukemia (AML). Venetoclax has also been used in non-myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk AML with a tolerable toxicity profile. However, the efficacy and safety of a venetoclax-containing myeloablative conditioning (MAC) allo-HSCT regimen for high-risk AML have not been evaluated. Objective To evaluate the safety and efficacy of a MAC regimen containing venetoclax for high-risk AML. Study design From 25 February 2021 to 4 September 2022, a total of 31 patients with high-risk AML who underwent allo-HSCT and a MAC regimen with venetoclax were analyzed. Results At the time of transplantation, 21 patients were in first complete remission (CR1), 4 were in a second complete remission (CR2), and 6 in non-remission (NR). Twenty-four patients (77.4%) were minimal residual disease (MRD)-positive before transplant. The FLT3-ITD gene mutation was present in 51.6% of patients. NUP98 rearrangement, MLL rearrangement or MLL-PTD and DEK::CAN fusion genes were found in 5 (16.1%), 7(22.6%) and 2 (6.5%) patients, respectively. Twenty-nine (93.6%) patients underwent haploidentical allo-HSCT. The median follow-up time was 278 days (range: 52–632 days). The 100-day cumulative incidence of grade 3 to 4 acute graft-versus-host disease (aGVHD) was 16.1% (95%CI, 7.2–36.0%). The 180-day cumulative incidence of moderate to severe chronic graft-versus-host disease (cGVHD) was 7.1% (95%CI, 1.9–26.9%). Cumulative incidence of 100-day cytomegalovirus (CMV) viraemia and 100-day Epstein-Barr virus (EBV) viraemia was 61.6% (95%CI, 46.5–81.4%) and 3.2% (95%CI, 0.4–22.2%), respectively. The 600-day overall survival (OS) and leukemia-free survival (LFS) were 80.9% (95%CI, 63.5–93.6%) and 81.3% (95%CI, 64.2–93.7%), respectively. The 600-day relapse incidence (RI) and non-relapse mortality (NRM) was 6.9% (95%CI, 1.8–26.3%) and 11.7% (95%CI, 3.9–35.0%). Conclusion Our study shows that the addition of venetoclax to a MAC allo-HSCT was feasible, safe and effective for high-risk AML patients.

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Section: Discussionmentioning

confidence: 99%

Addition of venetoclax to myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in high-risk AML

et al. 2023

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“…KMT2A is widely expressed in hematopoietic cells, including stem cells and progenitor cells. It has leukemogenic effects only after fusing with a variety of partner genes, such as AF4, AF9, ENL, AF10 and ELL ( 36 ). When MEN1 and LEDGF bind to the N-terminus of KMT2A, they further activate HOXA9 and HOXA10, which are usually upregulated in leukemia with KMT2A mutation.…”

Section: Marker Source 2: Chromosome Position Abnormality-related Mol...mentioning

confidence: 99%

Research progress on molecular biomarkers of acute myeloid leukemia

Yin

Wang²,

Jiang³

et al. 2023

Front. Oncol.

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Acute myeloid leukemia (AML) is the most common type of adult acute leukemia. The pathophysiology of the disease has been studied intensively at the cellular and molecular levels. At present, cytogenetic markers are an important basis for the early diagnosis, prognostic stratification and treatment of AML. However, with the emergence of new technologies, the detection of other molecular markers, such as gene mutations and epigenetic changes, began to play important roles in evaluating the occurrence and development of diseases. Recent evidence shows that identifying new AML biomarkers contributes to a better understanding of the molecular mechanism of the disease and is essential for AML screening, diagnosis, prognosis monitoring, and individualized treatment response. In this review, we summarized the promising AML biomarkers from four aspects, which contributing to a better understanding of the disease. Of course, it must be soberly aware that we have not listed all biomarkers of AML. Anyway, the biomarkers we mentioned are representative. For example, mutations in TP53, FLT3, and ASXL1 suggest poor prognosis, low remission rate, short survival period, and often require allogeneic hematopoietic stem cell transplantation. The CEBPA double mutation, NPM1 and CBF mutation suggest that the prognosis is good, the remission rate is high, the survival period is long, and the effect of chemotherapy or autotherapy is good. As for other mutations mentioned in the article, they usually predict a moderate prognosis. All in all, we hope it could provide a reference for the precise diagnosis and treatment of AML.

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Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia

Guo,

Kong

et al. 2023

Mol Biol Rep

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Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML

Cited by 7 publications

References 35 publications

Addition of venetoclax to myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in high-risk AML

Addition of venetoclax to myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in high-risk AML

Research progress on molecular biomarkers of acute myeloid leukemia

Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia

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